I’m Bipolar, You’re Bipolar

Early in the morning of December 13, 2006, police officers from the small town of Hull, MA, near Boston, arrived at the home of Michael and Carolyn Riley in response to an emergency call. Their four-year-old daughter, Rebecca, had been diagnosed with bipolar disorder two years earlier. When the officers reached the house, they found Rebecca sprawled out on the floor next to her teddy bear. She had died from an overdose of the medication cocktail prescribed to her by her psychiatrist, Dr. Kayoko Kifuji. At the time of her death, Rebecca was taking Seroquel®, a powerful antipsychotic drug, Depakote®, a no less powerful anticonvulsant and mood-stabilizing drug, and clonidine, a hypotensive drug used as a sedative.

Rebecca’s parents were charged with first-degree murder, but her doctor’s role must also be questioned. How could she have prescribed psychotropic medications normally intended for adults suffering from psychotic mania to a two-year-old? Yet the medical center where Rebecca had been treated issued a statement describing Dr. Kifuji’s treatment as “appropriate and within responsible professional standards.” In an interview with the Boston Globe, Dr. Janet Wozniak, director of the Pediatric Bipolar Program at Massachusetts General Hospital, went even further: “We support early diagnosis and treatment because the symptoms of [bipolar] disorder are extremely debilitating and impairing. […] It’s incumbent on us as a field to understand more which preschoolers need to be identified and treated in an aggressive way.” On July 1, 2009, a Plymouth County Grand Jury dropped all criminal charges against Dr. Kifuji.

How did we come to this? As the psychiatrist and historian David Healy points out in his latest book,Mania: A Short History of Bipolar Disorder (Johns Hopkins University Press, 2008), very few people had heard of bipolar disorder before 1980, when it was introduced in the DSM-III – the diagnostic manual of the American Psychiatric Association – and it was only in 1996 that a group of doctors from Massachusetts General Hospital, led by Joseph Biederman and Janet Wozniak, first proposed that some children diagnosed with attention-deficit/hyperactivity disorder (ADHD) might in fact suffer from bipolar disorder. But whoever googles “bipolar disorder” today is likely to learn that the illness has always been with us. It’s just a new name, we are told, for what used to be called manic depression, a severe mood disorder characterized by oscillations between states of manic hyperactivity and deep depression.

Healy has no trouble demonstrating that this is a retrospective illusion. “Manic-depressive insanity” (a term coined in 1899 by Emil Kraepelin) was a relatively rare illness – ten cases per one million people each year, Healy claims, or 0.001 percent of the general population. By contrast, the prevalence of bipolar disorder is supposed to be much higher. In 1994, the US National Comorbidity survey estimated that 1.3 percent of the American population suffered from bipolar disorder. Four years later, the psychiatrist Jules Angst upped the figure to 5 percent: 5,000 times higher than the figure suggested by Healy. Are we really talking about the same thing? Or did the name create a new thing?

Healy favors the second hypothesis. The term bipolar disorder, he explains, was simultaneously introduced in 1966 by Jules Angst and Carlo Perris, who proposed cleanly separating unipolar depressions from bipolar disorders (they were contradicting Kraepelin, who believed that both sets of disorders were presentations of one and the same manic-depressive illness). While their conceptual move has been hailed as a breakthrough, it is hard to understand what the point is – it muddles the diagnosis instead of clarifying it. In practice, how are we to distinguish a unipolar depression from a bipolar disorder in a patient who has yet to experience a manic episode? Nonetheless, instead of seeing this incoherence as a reason for rejecting the new paradigm, psychiatrists have since done their utmost to patch it up with all sorts of ad hoc innovations.

First a distinction was made between “bipolar disorder I,” which applied to patients hospitalized for both depressive and manic episodes, and a brand new “bipolar disorder II,” which referred to patients hospitalized solely for a depressive episode. In other words, any person hospitalized for depression could now be diagnosed as bipolar. Then the reference to hospitalization was dropped for bipolar disorder II, which meant it could now include less severe forms of depression and hyperactivity, as well as all sorts of neurotic disorders that Kraepelin would never have dreamed of calling manic-depressive insanity. One now speaks of a “bipolar spectrum,” which includes, along with bipolar disorders I and II, cyclothymia (a mild form of bipolar II) and bipolar disorder “not otherwise specified” (an all-purpose category in which practically any affective instability can be placed) – to which some add bipolar disorders II ½, III, III ½, IV, V, VI, and even a very accommodating “subthreshold bipolar disorder.”

The category has expanded so much that it would be difficult to find anyone who couldn’t be described as “bipolar,” especially now that the diagnosis is liberally applied to all ages. Conventional wisdom once had it that manic depression burns out with age, but geriatric bipolar disorder is now the talk of psychiatric congresses. Elderly people who are depressed or agitated find themselves being diagnosed with bipolar disorder for the first time in their lives and are prescribed antipsychotics or anticonvulsants that have the potential to drastically shorten their life expectancy: according to David Graham, an expert from the US Food and Drug Administration (FDA), these psychotropic medications are responsible for the deaths of some 15,000 elderly people each year in the United States. Likewise, it has been assumed since the work of Biederman and Wozniak that bipolar disorder can strike in early childhood and not just with the onset of adolescence. As a result, the prevalence of pediatric bipolar disorder multiplied by a factor of 40 between 1994 and 2002.

How, then, did we come to apply such a serious diagnosis to vaguely depressed or irritable adults, to unruly children and to nursing home residents? Is it simply that psychiatric science has progressed and now allows us to better detect an illness that had previously been ignored or misunderstood? Healy has another, more cynical explanation: The never-ending expansion of the category of bipolar disorder benefits large pharmaceutical companies eager to sell medications marketed with the disorder in mind. Psychiatric research doesn’t evolve in a vacuum. Behind the psychiatrists’ constant redrawing of the map of mental illnesses in a sincere effort at better understanding, there are enormous financial and industrial interests that steer research in one direction rather than another. For researchers, mental illnesses are realities whose contours they attempt to define; for pharmaceutical companies, they are markets that can, thanks to marketing and branding techniques, be redefined, segmented and extended in order to make them ever more lucrative. The uncertainties of the psychiatric field present in this respect a magnificent commercial opportunity, since illnesses can always be tailored to better sell a particular molecule under a particular patent.

In the case of bipolar disorder, this conceptual gerrymandering has involved stretching and diluting the definition of what used to be called manic-depressive illness so that it might include depression and other mood disorders, thus creating a market for “atypical” antipsychotic medications such as Lilly’s Zyprexa®, AstraZeneca’s Seroquel® or Janssen’s Risperdal®. Even though these medications were initially approved only for the treatment of schizophrenia and acute manic states, they were marketed for the treatment of bipolar disorder and by extension mood disorders in general. The same was done to anticonvulsant medications, which are strong sedatives prescribed for epileptic attacks. In 1995 Abbott Laboratories succeeded in obtaining a license to offer its anticonvulsant drug Depakote® for the treatment of mania. Depakote®, however, was marketed not as an anticonvulsant but as a “mood stabilizer” – a term without any clinical meaning that is misleading insofar as it suggests a preventive action against bipolar disorder that has never been established in any study.

In the wake of this brilliant terminological innovation, other anticonvulsants such as Warner Lambert/Parke Davis’s Neurontin® were aggressively marketed for mood disorders when they hadn’t been approved even for manic states. But what did it matter, since the meteoric success of the concept of “mood stabilization” made this step useless? The suggestion to doctors was that they prescribe anticonvulsants or atypical antipsychotics to “stabilize” the moods of depressive patients who had never before displayed any manic hyperactivity, the idea being that these people had been misdiagnosed as suffering from unipolar depression while in fact being bipolar. Anyone who knows how lucrative the market was for selective serotonin reuptake inhibitor (SSRI) antidepressants such as Prozac® or Paxil® in the 1990s will immediately see the point of the exercise. While most SSRIs are now off patent, the market for atypical antipsychotics is currently worth $18 billion – twice as much as that of antidepressants in 2001.

It is easy to see that the redefinition of manic depression into the much wider concept of mood disorders neatly mirrors the marketing of anticonvulsants and atypical antipsychotics as mood stabilizers. The question, of course, is whether the pharmaceutical industry’s marketers actually created bipolar disorder or merely exploited tentative psychiatric research. Strictly speaking, we must grant it was opportunism: The research of Angst and Perris on bipolar disorder dates from 1966, well before the development of atypical antipsychotics and “mood stabilizers.” But the reality of the contemporary medical-industrial complex is that their hypothesis would not have survived, let alone prospered, had it not been “recruited” at a particular moment by the pharmaceutical industry and thrust forcefully on the public with the help of the most sophisticated marketing and advertising techniques.

This is what Healy calls the “manufacture of consensus”: By subsidizing one research program instead of another, one conference or symposium, one journal, one publication, one learned society and so on, the pharmaceutical industry doesn’t just make precious allies among the “key opinion leaders” of the medical establishment, it also gains a very efficient means of steering the academic discussion toward the illnesses that interest it at any given moment. Healy provides a detailed description of how bipolar disorder was launched at the end of the 1990s, from the avalanche of publications ghostwritten by specialized PR agencies to the sponsoring of bipolar patient advocacy groups and the creation of websites where people could fill out “mood assessment questionnaires” that inevitably dispatched them to the nearest doctor. Following this marketing blitz, no one could ignore bipolar disorder any longer. As a Practical Guide to Medical Education intended for industry marketers explains, “It is essentially like setting a snowball rolling down a hill. It starts with a small core of support: maybe a few abstracts presented at meetings, articles in key journals, focuses for discussion amongst ‘leading experts’ […] and by the time it reaches the bottom of the hill the noise should be coming from all sides and sources.” Pharmaceutical companies today launch diseases in the way fashion companies launch a new brand of jeans: creating needs that align with industrial strategies and the duration of patents.

The techniques Healy describes are the same as those used by the pharmaceutical industry to sell, or oversell, conditions as diverse as depression, osteoporosis, hypertension, social phobia, metabolic syndrome, high cholesterol, attention-deficit/hyperactivity disorder, fibromyalgia, premenstrual dysphoric disorder, panic attacks, restless leg syndrome and so forth. In each case the existence and risks of one condition or another are amplified in order to better persuade us to swallow chemical products that may be either useless or, often, potentially toxic.

In the case of bipolar disorder, the medications on offer come with significant risks. Anticonvulsants are liable to cause kidney failure, obesity, diabetes and polycystic ovary syndrome, and they are among the most teratogenic drugs. Atypical antipsychotics, once reputed to be less toxic than first-generation “typical” antipsychotics, are now known to have very serious side effects: significant weight gain, diabetes, pancreatitis, stroke, heart disease and tardive dyskinesia (a condition involving incapacitating involuntary movements of the mouth, lips and tongue). They can, in some circumstances, cause neuroleptic malignant syndrome, a life-threatening neurological disorder, and akathisia, whose sufferers experience extreme internal restlessness and suicidal thoughts. Prescribing such toxic medications to patients suffering acute mania may be unavoidable, but as a prophylactic to be given to depressed pensioners and hyperactive kids?

A series of prominent lawsuits has been brought over the past few years in the United States against the manufacturers of anticonvulsants and atypical antipsychotics for having hidden their side effects and for having marketed them “off label” to patient populations not approved by the FDA. The sums paid out in fines or settlements by the companies involved are staggering (a total of $2.6 billion for the illegal marketing of Zyprexa® by Lilly, for example), and they give an idea of how disastrous the effects of the medications actually have been. In a related development, Dr. Joseph Biederman, director of the Johnson & Johnson Center for Pediatric Psychopathology Research at Massachusetts General Hospital and the main academic advocate of pediatric bipolar disorder, has been subpoenaed in a federal investigation to account for the $1.6 million he received between 2000 and 2007 from Johnson & Johnson and other pharmaceutical companies likely to benefit directly from his research.

But the marketing of bipolar disorder itself has not been put on trial, and probably never will be. This is the perfect crime. Bipolar disorder I, II, III, etc., remain on the books and doctors continue to exercise their freedom of judgment in prescribing Zyprexa® and Seroquel® off label to their “bipolar” patients. An extended release version of Seroquel®, Seroquel XR®, was approved in December 2009 by the FDA for the treatment of depression. As for sales of Zyprexa®, they are up 2 percent compared to 2007, when the medication generated $4.8 billion in sales.

Who remembers Rebecca Riley now?

Mikkel Borch-Jacobsen teaches comparative literature at the University of Washington. His latest book is Making Minds and Madness: From Hysteria to Depression(Cambridge University Press). A longer version of this article was published on October 7, 2010 in the London Review of Books.[cherry_banner image=”4701″ title=”Adbusters #94″ url=”http://subscribe.adbusters.org/collections/back-issues/products/ab94″ template=”issue.tmpl”]Post Normal[/cherry_banner]